The application describes a continuing plan designed to elucidate the neuronal and synaptic organization of nigral, pallidal and cerebellar projection territories in the motor thalamus of a nonhuman primate. Aside from the data we have collected, there is little information available on the organization of neuronal circuitry in these thalamic regions in primates. However, the existing information on connectivity points to essential differences between primate and nonprimate species with respect to the afferent/efferent organization of the motor thalamus, and our electronmictoscopic investigations reveal species-specific ultrastructural features as well. This emphasizes the need and importance of further in- depth studies on neuronal and synaptic organization of the primate motor thalamus. The major specific aims of the proposed studies arise from the findings of the previous funding period and include identification of ultrastructural features and synaptic sites of additional subcortical afferents to the motor thalamic nuclei such as superior colliculus projections to the nigral territory and thalamic reticular nucleus connections to nigral, pallidal and cerebellar regions of the motor thalamus. Additional aims include identification of terminals and synaptic sites of afferents from individual deep cerebellar nuclei, and further in-depth analysis of the pallidal territory of the motor thalamus. The studies will be carried out with various neuroanatomical techniques at the EM level. The major emphasis will be on the use of EM autoradiography and computer-assisted quantitative morphometric analysis of density and distribution of various types of synaptic boutons on soma-dendritic membrane of thalamocortical projection neurons and local circuit neurons. Anterograde labeling with WGA-HRP and Phaseolus vulgaris leucogglutinin will also be used in some experiments as well as immunocytochemical visualization of glutamic acid decarboxylase (GAD) and retrograde labeling with WGA-HRP. The studies will provide new and much needed data on the fine structural organization of the ascending output pathways from the basal ganglia and cerebellum in primates, and the role of the thalamic circuits in the processing of the information carried by these neural systems. The results will contribute to the understanding of the mechanisms of normal and abnormal movements as well as complex behaviors involving the motor system. Our clinical interests center on dyskinetic disorders which debilitate humans of all ages and which constitute one of the major neurological problems in the elderly. With only a few exceptions, a therapeutic impasse exists in their treatment. This is aggravated in part by limited basic research efforts specifically directed toward the motor thalamus. The aims of the research proposed, and our commitment, centers on the goal of reversing this situation.